This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3bar

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="3bar" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bar, resolution 1.90&Aring;" /> '''Crystal structure of...)
Current revision (12:05, 30 August 2023) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3bar.jpg|left|200px]]<br /><applet load="3bar" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="3bar, resolution 1.90&Aring;" />
 
-
'''Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP'''<br />
 
-
==Overview==
+
==Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP==
-
Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug, resistance. In Plasmodia, orotidine 5'-monophosphate decarboxylase, (ODCase) is an essential enzyme for the de novo synthesis of uridine, 5'-monophosphate. Impairing ODCase in these pathogens is a promising, strategy to develop novel classes of therapeutics. Encouraged by our, recent discovery that 6-iodo uridine is a potent inhibitor of P., falciparum, we investigated the structure-activity relationships of, various C6 derivatives of UMP. 6-Cyano, 6-azido, 6-amino, 6-methyl, 6-, N-methylamino, and 6- N, N-dimethylamino derivatives of uridine were, evaluated against P. falciparum. The mononucleotides of 6-cyano, 6-azido, 6-amino, and 6-methyl uridine derivatives were studied as inhibitors of, plasmodial ODCase. 6-Azidouridine 5'-monophosphate is a potent covalent, inhibitor of P. falciparum ODCase. 6-Methyluridine exhibited weak, antimalarial activity against P. falciparum 3D7 isolate. 6- N-Methylamino, and 6- N, N-dimethylamino uridine derivatives exhibited moderate, antimalarial activities.
+
<StructureSection load='3bar' size='340' side='right'caption='[[3bar]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3bar]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BAR FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bar OCA], [https://pdbe.org/3bar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bar RCSB], [https://www.ebi.ac.uk/pdbsum/3bar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bar ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/Q8IJH3_PLAF7 Q8IJH3_PLAF7]
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ba/3bar_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bar ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug resistance. In Plasmodia, orotidine 5'-monophosphate decarboxylase (ODCase) is an essential enzyme for the de novo synthesis of uridine 5'-monophosphate. Impairing ODCase in these pathogens is a promising strategy to develop novel classes of therapeutics. Encouraged by our recent discovery that 6-iodo uridine is a potent inhibitor of P. falciparum, we investigated the structure-activity relationships of various C6 derivatives of UMP. 6-Cyano, 6-azido, 6-amino, 6-methyl, 6- N-methylamino, and 6- N, N-dimethylamino derivatives of uridine were evaluated against P. falciparum. The mononucleotides of 6-cyano, 6-azido, 6-amino, and 6-methyl uridine derivatives were studied as inhibitors of plasmodial ODCase. 6-Azidouridine 5'-monophosphate is a potent covalent inhibitor of P. falciparum ODCase. 6-Methyluridine exhibited weak antimalarial activity against P. falciparum 3D7 isolate. 6- N-Methylamino and 6- N, N-dimethylamino uridine derivatives exhibited moderate antimalarial activities.
-
==About this Structure==
+
Structure-Activity Relationships of C6-Uridine Derivatives Targeting Plasmodia Orotidine Monophosphate Decarboxylase.,Bello AM, Poduch E, Liu Y, Wei L, Crandall I, Wang X, Dyanand C, Kain KC, Pai EF, Kotra LP J Med Chem. 2008 Feb 14;51(3):439-448. Epub 2008 Jan 12. PMID:18189347<ref>PMID:18189347</ref>
-
3BAR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=U5P:'>U5P</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] Known structural/functional Sites: <scene name='pdbsite=AC1:U5p Binding Site For Residue A 3000'>AC1</scene> and <scene name='pdbsite=AC2:U5p Binding Site For Residue B 3000'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BAR OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
Structure-Activity Relationships of C6-Uridine Derivatives Targeting Plasmodia Orotidine Monophosphate Decarboxylase., Bello AM, Poduch E, Liu Y, Wei L, Crandall I, Wang X, Dyanand C, Kain KC, Pai EF, Kotra LP, J Med Chem. 2008 Jan 12;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18189347 18189347]
+
</div>
-
[[Category: Orotidine-5'-phosphate decarboxylase]]
+
<div class="pdbe-citations 3bar" style="background-color:#fffaf0;"></div>
-
[[Category: Plasmodium falciparum]]
+
== References ==
-
[[Category: Single protein]]
+
<references/>
-
[[Category: Bello, A.M.]]
+
__TOC__
-
[[Category: Kotra, L.P.]]
+
</StructureSection>
-
[[Category: Lau, W.]]
+
[[Category: Large Structures]]
-
[[Category: Liu, Y.]]
+
[[Category: Plasmodium falciparum 3D7]]
-
[[Category: Pai, E.F.]]
+
[[Category: Bello AM]]
-
[[Category: Poduch, E.]]
+
[[Category: Kotra LP]]
-
[[Category: U5P]]
+
[[Category: Lau W]]
-
[[Category: 6-azido-ump]]
+
[[Category: Liu Y]]
-
[[Category: covalently]]
+
[[Category: Pai EF]]
-
[[Category: crystal structure]]
+
[[Category: Poduch E]]
-
[[Category: lyase]]
+
-
[[Category: orotidine 5'-phosphate decarboxylase]]
+
-
[[Category: plasmodium falciparum]]
+
-
[[Category: pyrimidine biosynthesis]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 11:03:13 2008''
+

Current revision

Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP

PDB ID 3bar

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3bar"
Personal tools